Our goal in this project is to understand the mechanisms by which steroid receptor proteins regulate the expression of eukaryotic genes; specifically, we are examining in cultured cells the regulation of mammary tumor virus (MTV) genes by dexamethasone, a synthetic glucocorticoid. We have demonstrated directly that in whole cells dexamethasone stimulates the accumulation of MTV RNA by selectively and rapidly increasing its rate of synthesis. Moreover, we have defined conditions in which intact nuclei isolated from these cells appear to maintain with some degree of fidelity the program of gene transcription established in the whole cell. In addition, we have infected a line of rat hepatoma cells with MTV. In general, the newly integrated MTV genes in clones of infected cells are stimulated by dexamethasone to increase their rates of MTV RNA synthesis; many of these clones display a reduced inducibility by dexamethasone of normally responsive host genes.